The objective of this research is to study the biological consequences of disruption by lesions or pharmacological methods of specific central nervous system pathways in the neonatal animal. The ontogenesis of these central neuronal systems is to be modified or prevented by surgical or pharmacological methods at various points in time following birth. We then intend to study these animals as they mature for the neurochemical, neurophysiological, neuroanatomic, and behavioral consequences of this early disruption of the development of the nervous system. Comparative studies utilizing similar surgical or pharmacologic insults in the adult animal will also be performed. The objective of making such comparisons is to allow one 1) to determine if a critical time period exists during which a particular neurochemical system has a significant effect on the ontogeny of the remaining functional systems in brain, 2) the nature of adaptive responses to injury in the neonatal and adult brain, 3) to obtain a better understanding of the fundamental relationships between neuroanatomic and neurochemical ontogenesis and function. The results obtained in this study may eventually enable one to design better treatment of central nervous system disease with genetic or environmental etiologies.